title: A role for platelet TRPC channels in the Ca2+ response that induces procoagulant activity.
abstract: After vascular injury, platelets are rapidly activated by collagen and other agonists, causing them to adhere and aggregate to prevent blood loss. In addition, phosphatidylserine (PS) exposure on the platelet surface accelerates thrombin formation by the coagulation pathway. Thrombin is a potent platelet agonist and converts fibrinogen to fibrin, thereby stabilizing the platelet plug. PS exposure during hemostasis and thrombosis results from a sustained cytosolic Ca(2+) increase; however, the underlying Ca(2+) mobilization pathways have remained unclear. Store-operated Orai1 channels provide substantial, prolonged Ca(2+) influx after inositol trisphosphate-dependent release, and anoctamin 6 (TMEM16F) may operate as a Ca(2+)-activated, Ca(2+)-permeable channel in addition to its scramblase activity that exteriorizes PS. A new study shows that Na(+) entry, resulting from coactivation of the transient receptor potential (TRP) nonselective cation channels TRPC3 and TRPC6, followed by reverse-mode operation of Na(+)/Ca(2+) exchangers, is an important mechanism for the increase in cytosolic Ca(2+) that triggers PS exposure, particularly during combined thrombin and collagen stimulation.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK. mpms1@le.ac.uk
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Mahaut-Smith
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010718:Phosphatidylserines / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; D013917:Thrombin; D002118:Calcium